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Biomedical subjects

M R de Leval

Publications and source records attributed to M R de Leval.

At least 55 records · Page 3Linked to original sources

Innervation of human atrioventricular and arterial valves.

BACKGROUND: Limited information exists on the innervation of human cardiac valves and the relationship of nerve fibers and terminals with functional elements within leaflets. METHODS AND RESULTS: We examined human AV and arterial valves, obtained postmortem and at surgery, using quantitative immunohistochemical, histochemical, and confocal microscopic techniques. Significant differences in nerve density and distribution were found both between and within cardiac valves. Nerve density within the anterior leaflet of the mitral valve, for example, was twofold greater than that in the posterior leaflet (P < .001). Nerves within the AV valves were situated in the atrial layer and extended over the proximal and medial portions of the leaflets, whereas those in the arterial valves were situated in the ventricular layer. No nerves reached either the free edge or the fibrous core of the leaflets. The arterial valves displayed a similar density of innervation, except for the noncoronary leaflet of the aortic valve in which the innervation was attenuated (P < .01). The innervation of aortic valvar leaflets was age dependent. Nerve terminal arborizations, arising from myelinated nerves and exhibiting variable morphology, were detected in all four cardiac valves and in some tendinous cords. Nerve terminals exhibited either acetylcholinesterase activity or tyrosine hydroxylase and neuropeptide Y immunoreactivity. Varicose nerve fibers occurred in close physical proximity to valvar endothelial, smooth muscle, and fibroblast cells. CONCLUSIONS: Human cardiac valves have distinct patterns of innervation that comprise both primary sensory and autonomic components. The presence of distinct nerve terminals and the close association of varicose nerve fibers with endothelial, smooth muscle, and fibroblast cells suggest a possible neural involvement in the control of valvar function.

Acetylcholinesterase↗

A numerical fluid mechanical study of repaired congenital heart defects. Application to the total cavopulmonary connection.

A computational fluid dynamics study based on the application of the finite element method has been performed to investigate the local hemodynamics of the total cavopulmonary connection. This operation is used to treat congenital malformations of the right heart and consists of a by-pass of the right ventricle. In this paper the adopted methodology is presented, together with some of the preliminary results. A three-dimensional parametric model of the connection and a lumped-parameter mechanical model of the pulmonary circulation have been developed. The three-dimensional model has been used to simulate the local fluid dynamics for different designs of the connection, allowing a quantitative evaluation of the dissipated energy in each of the examined configurations. The pulmonary afterload of the three-dimensional model has been reproduced by coupling it with the pulmonary mechanical model. The results show that, from a comparative point of view, the energetic losses can be greatly reduced if a proper hydraulic design of the connection is adopted, which also allows control of the blood flow distribution into the lungs.

Algorithms↗

Nitric oxide might reduce the need for extracorporeal support in children with critical postoperative pulmonary hypertension.

BACKGROUND: Postoperative pulmonary hypertension is a life-threatening, yet reversible complication of congenital heart operations. Although inhaled nitric oxide (iNO), a selective pulmonary vasodilator, has been shown extensively to improve short-term oxygenation and hemodynamic indices in these patients, its influence on patient outcome has not been evaluated. The purpose of this study was to assess retrospectively whether patients who fulfilled our criteria for extracorporeal life support (ECLS) for critical postoperative pulmonary hypertension still required ECLS after the administration of iNO therapy. METHODS: Since January 1992, 10 patients (age 3 days to 10 months) fulfilled the criteria at our institution for ECLS for postoperative pulmonary hypertension. Of these, 5 could not be separated from cardiopulmonary bypass because of pulmonary hypertension, and 5 had critical pulmonary hypertension (pulmonary arterial pressure approaching systemic arterial pressure) causing severe cardiopulmonary compromise. RESULTS: Six of the 10 ECLS candidates had a sustained response to iNO and survived to discharge from the hospital, without the need for rescue ECLS. Three patients still required ECLS after 30 minutes, 4 hours, and 8 hours of beginning iNO because of failing cardiac output, and 2 survived. The remaining patient died after 5 days of iNO therapy, but was no longer a candidate for ECLS because of sepsis and multiorgan system failure. CONCLUSIONS: Children with critical pulmonary hypertension unresponsive to maximal conventional treatment may be managed successfully with iNO without the need for rescue ECLS. A trial of iNO should therefore be given before the use of ECLS in these patients.

Administration, Inhalation↗

Expanded PTFE membrane to prevent cardiac injury during resternotomy for congenital heart disease.

BACKGROUND: Resternotomy for repair of congenital cardiac defects can result in cardiac injury. Closure of the pericardium during the initial operation may prevent this, and several pericardial substitutes have been tried, with variable results, in patients in whom primary pericardial closure is not possible. We conducted a multicenter observational study of the use of the expanded polytetrafluoroethylene membrane (Preclude Pericardial Membrane, formerly called the Gore-Tex Surgical Membrane; W. L. Gore & Associates, Flagstaff, AZ) in patients likely to undergo reoperation for treatment of congenital heart disease. METHODS: Data were collected retrospectively on all patients in whom the expanded polytetrafluoroethylene membrane was inserted at the initial operation for congenital heart disease at 12 centers in 1984 to 1993. RESULTS: A total of 1,085 patients (mean age, 55 +/- 2.5 months) received the membrane. During follow-up ranging from 1.3 to 10.5 years, 105 reoperations were performed. Injury during resternotomy occurred in only 1 patient (1% of reoperations). There were no membrane-related deaths or complications in the entire series of 1,085 patients. CONCLUSIONS: The expanded polytetrafluoroethylene membrane was safe and effective in helping to prevent cardiac injury during resternotomy for treatment of congenital heart disease.

Child, Preschool↗

Is a high-risk biventricular repair always preferable to conversion to a single ventricle repair?

OBJECTIVES: The aim of this report is to examine the short-and intermediate-term outcome of a complex biventricular repair compared with a single ventricle repair in patients with two functional ventricles. PATIENT POPULATION: Since 1986, 34 patients with atrioventricular concordance or discordance, ventriculoarterial discordance, ventricular septal defect, and pulmonary stenosis or atresia have undergone biventricular repair (group I). Another group of 16 patients (group II) with the same diagnoses have undergone a single ventricle repair consisting of a total cavopulmonary connection because of either a straddling atrioventricular valve (11 patients) or an uncommitted ventricular septal defect (5 patients). RESULTS: The mean length of follow-up was 3.9 years in group I and 3.0 years in group II. Freedom from reoperation at 7 years was 45.5% in group I and 100% in group II (p = 0.014). The actuarial estimate of survival at 7 years was 68.0% in group I and 93.8% in group II (p = 0.048). CONCLUSION: Short- and intermediate-term morbidity and mortality were greater in patients undergoing a biventricular repair than in a similar group of patients undergoing total cavopulmonary connection. It is unknown whether the long-term results of a total cavopulmonary connection in patients with two ventricles are as good as those obtained with a biventricular approach. However, there may be situations in which the short- and intermediate-term risks of a complex biventricular repair may outweigh the long-term disadvantages of a single ventricle approach.

Actuarial Analysis↗

Mixed total pulmonary venous drainage: still a surgical challenge.

OBJECTIVE: The aim of this report is to review the surgical experience of a single institution with a relatively large series of patients with mixed total pulmonary venous drainage. PATIENT POPULATION: Between January 1, 1971, and December 31, 1994, 232 patients with total pulmonary venous drainage underwent surgical correction. Twenty of these patients (8.6%) had mixed type total pulmonary venous drainage. Ages at operation ranged from 1 day to 46 months, with a median of 2.3 months. RESULTS: Both cardiac catheterization and echocardiography were performed before operation in 12 patients. Four patients underwent only cardiac catheterization, and another four patients underwent only echocardiography. The sensitivity and specificity for catheterization were 94% and 99%, respectively; they were 31% and 100%, respectively, for echocardiography. Severe pulmonary venous obstruction was present in three patients, all of whom underwent emergency operation. Three patients (15%), all of whom had preoperative pulmonary venous obstruction, died after operation. There were two late deaths, one of pulmonary vein stenosis and the other of probable pulmonary hypertension. The actuarial survival at 10 years was 73% for all patients; patients who survived the initial operation had a 10-year survival of 87%. CONCLUSION: The diagnosis of mixed total pulmonary venous drainage can be difficult to establish by echocardiography or at the time of operation. For patients in stable condition, cardiac catheterization may be considered if fewer than three pulmonary veins are identified by echocardiography. Pulmonary venous obstruction is relatively infrequent in this group of patients but when present impacts patient survival significantly. The long-term results with this lesion are excellent.

Actuarial Analysis↗

Use of computational fluid dynamics in the design of surgical procedures: application to the study of competitive flows in cavo-pulmonary connections.

Computational fluid dynamic methods based on a finite-element technique were applied to the study of (1) competition of flows in the inferior and superior venae cavae in total cavopulmonary connection, and (2) competition between flow in the superior vena cava and forward flow from a stenosed pulmonary artery in bidirectional cavopulmonary anastomosis. Models corresponding to various degrees of offsetting and shape of the inferior vena caval anastomosis were simulated to evaluate energy dissipation and flow distribution between the two lungs. A minimal energy loss with optimal flow distribution between the two lungs was obtained by enlarging the inferior vena caval anastomosis toward the right pulmonary artery. This modified technique of total cavopulmonary connection is described. A computational model of the operation was developed in an attempt to understand the mechanisms of postoperative failure. In tight pulmonary artery stenosis (75%), the pulsatile forward flow is primarily directed to the left pulmonary artery, with little influence on superior vena caval pressure and the right pulmonary artery. Pulsatile forward flows corresponding to 15%, 30%, 45%, and 60% of the systemic artery output increased the mean pulmonary artery and superior vena caval pressures by 1, 1.7, 2.4, and 3.6 mm Hg, respectively. Although the modeling studies were not able to determine the cause of postoperative failure, they emphasize the impact of local geometry on flow dynamics. More simulations are required for further investigation of the problem.

Anastomosis, Surgical↗

An alternative method for repair of aortico-left ventricular tunnel associated with severe aortic stenosis presenting in a newborn.

Although a rare congenital anomaly, aortico-left ventricular tunnel (ALVT) presents in infants as severe aortic regurgitation which can be successfully corrected at the time of diagnosis. In this neonatal case of ALVT, the dominant clinical presentation was of severe aortic stenosis. Ultimately, aortic root replacement with an aortic homograft was required to repair both the ALVT and the dysplastic, stenotic aortic valve.

Aorta, Thoracic↗

A computational pulsatile model of the bidirectional cavopulmonary anastomosis: the influence of pulmonary forward flow.

The bidirectional cavopulmonary anastomosis (BCPA or bidirectional Glenn) is an operation to treat congenital heart diseases of the right heart by diverting the systemic venous return from the superior vena cava to both lungs. The main goal is to provide the correct perfusion to both lungs avoiding an excessive increase in systemic venous pressure. One of the factors which can affect the clinical outcome of the surgically reconstructed circulation is the amount of pulsatile blood flow coming from the main pulmonary artery. The purpose of this work is to analyse the influence of this factor on the BCPA hemodynamics. A 3-D finite element model of the BCPA has been developed to reproduce the flow of the surgically reconstructed district. Geometry and hemodynamic data have been taken from angiocardiogram and catheterization reports, respectively. On the basis of the developed 3-D model, four simulations have been performed with increasing pulsatile blood flow rate from the main pulmonary artery. The results show that hemodynamics in the pulmonary arteries are greatly influenced by the amount of flow through the native main pulmonary artery and that the flow from the superior vena cava allows to have a similar distribution of the blood to both lungs, with a little predilection for the left side, in agreement with clinical postoperative data.

Blood Flow Velocity↗

[Human factors and heart surgery: a Cartesian dream].

It is postulated that high technology medicine can be assimilated to complex socio-technical systems such as the aviation industry, nuclear power or chemical plants etc. It is proposed to apply to cardiac surgery the techniques of human reliability and human error analysis that have been acquired over the past two decades to enhance safety in those areas of high technology. It is now widely accepted that in complex socio-technical systems accidents are due to human factors in 60-80% of the cases. Accident theories and, in particular theories of organisational accidents, have been applied prospectively to negative surgical outcomes in an attempt to understand their causation ad to establish defence mechanisms to prevent them or at least mitigate their consequences. The philosophical issues raised by this endeavour will be outlined.

Cardiac Surgical Procedures↗

Distribution, morphology, and neurochemistry of endocardial and epicardial nerve terminal arborizations in the human heart.

BACKGROUND: The heart contains a variety of morphologically distinct nerve terminals known to influence cardiac function. Little is known about the distribution, morphology, and neurochemistry of these terminals in the human heart. METHODS AND RESULTS: We examined the entire endocardial and epicardial surfaces of infant and adult hearts obtained postmortem and at transplantation using immunohistochemical and histochemical staining of whole-mount preparations in conjunction with confocal and fluorescence microscopy. Terminals arising from nerve fibers (diameter, 6 to 10 microns) immunoreactive for myelin basic protein were identified in the atrial endocardium, epicardium, and coronary sinus, and four types were distinguished by differences in immunostained nerve area (range, 358 to 797 microns 2) and dispersion (range, 620 to 4684 microns 2). These terminals displayed immunoreactivity for tyrosine hydroxylase, neuropeptide Y, and the general neural marker protein gene product 9.5. Acetylcholinesterase (AChE) activity was detected in < 5% of endocardial terminals and in no epicardial terminals arising from myelinated fibers. The latter were observed in close proximity to mesothelial cells, and nerve fibers supplying these terminals were found to be associated with local ganglia. A distinct population of terminals (mean stained area, 35 microns 2; 18 to 53 microns 2, 95% CI; and mean dispersion, 59 microns 2; 38 to 80 microns 2, 95% CI) was demonstrated to arise from nonmyelinated fibers (mean diameter, 2.5 microns; 2.2 to 2.8 microns, 95% CI) in the endocardial plexus of the atria and left ventricle and were predominantly AChE-positive. CONCLUSIONS: Specialized nerve terminals are distributed more widely in the human heart than has been described in experimental animals. These terminals express either AChE activity or tyrosine hydroxylase and neuropeptide Y immunoreactivity, suggesting that acetylcholine, catecholamines, and neuropeptide Y may be present in sensory and autonomic nerves in the human heart.

Acetylcholinesterase↗

Orthotopic heart transplantation in situs inversus.

The case of a successful orthotopic heart transplantation for complete situs inversus with double-inlet left ventricle and anomalies of the systemic venous return is reported. A piece of aortic homograft and a composite conduit made of the recipient right atrium and pericardium were used to connect, respectively, the left superior vena cava and the hepatic veins to the right-sided atrium of the donor heart.

Adolescent↗

Vascular and contractile function and tissue metabolites after prolonged hypothermic ischaemia and reperfusion: comparison of single- versus multi-dose infusions with two cardioplegic solutions in blood-perfused neonatal pig hearts.

The effects of single- and multi-dose cardioplegia on post-ischaemic vascular function and contractile activity were compared in 69 blood-perfused neonatal pig hearts, as were the protective properties of two different cardioplegic solutions. Hearts (n = 6 or 9 per group) from neonatal (3-5 days old) pigs were excised, arrested with a 2 min infusion (at 15 degrees C) of St Thomas' Hospital cardioplegic solution number 1 (STH1) or number 2 (STH2), and then maintained in a state of hypothermic (15 degrees C) ischaemia for 6 or 8 h. Hearts in the multi-dose groups received cardioplegia every hour (2 min at 15 degrees C). At the end of ischaemia all hearts were reperfused (60 +/- 2 mmHg perfusion pressure) for 40 min with blood from a support pig. Systolic and diastolic functions were assessed with an intraventricular balloon, and endothelial and smooth muscle functions by measuring the response to infusions of defined concentrations of acetylcholine (8, 16 and 32 micrograms/min) and glyceryl trinitrate (40, 80 and 160 micrograms/min). Hearts (n = 9) not subjected to ischaemia were perfused for the same duration to act as aerobic controls. At the end of the perfusion period, hearts were frozen and taken for metabolite analysis. After 8 h ischaemia, the recovery of left ventricular developed pressure was greatest in the multi-dose STH1 and single-dose STH2 groups (113 +/- 6 and 117 +/- 6 mmHg, respectively, v 128 +/- 9 mmHg in aerobic controls, at an end-diastolic pressure of between 3 and 9 mmHg; P = N.S.) and the poorest in the single-dose STH1 group (92 +/- 5 mmHg; P < 0.05 v controls). The recovery of diastolic function was greatest in the multi-dose STH2 group and again poorest in the single-dose STH1 group (left ventricular end-diastolic pressure 1 +/- 2 and 30 +/- 10 mmHg, at a ventricular volume of 3.0 ml, v -1 +/- 1 mmHg in aerobic controls). Vascular responses to acetylcholine and glyceryl trinitrate and the myocardial high-energy phosphates content were better preserved in multi-dose groups and with STH2. Inter-group differences were less when the duration of ischaemia was reduced to 6 h. In conclusion, the neonatal pig heart was best preserved with multi-dose cardioplegia and STH2 was more efficacious than STH1. However, not all indices were optimally protected by multi-dose STH2. Thus, the best protection of systolic function was obtained with multidose STH1 and this was followed by single-dose STH2. Diastolic function was best preserved with multi-dose STH2 as were vascular function and high-energy phosphates.

Animals↗

Results of heart-lung transplantation in children with cystic fibrosis.

Children with cystic fibrosis represent the largest group referred for, and undergoing, heart-lung transplantation at our institute. Between June 1988 and July 1993, 76 patients were accepted for transplantation, of whom 25 were transplanted, while a further 36 died waiting. Those transplanted ranged from 5-18 years of age and included 13 males and 12 females. Organs were used from donors matched by ABO blood group, size and cytomegalovirus (CMV) status. Post-transplant maintenance immunosuppression comprised cyclosporin A, azathioprine and prednisolone. Anti-thymocyte globulin and high dose methylprednisolone were given peri-operatively and for acute rejection episodes. Actuarial survival was 67% at 1 year, 61% at 2 years and 54% at 3 years. Obliterative bronchiolitis (OB) has occurred in 13 patients (52%) and was the major cause of mortality and morbidity. In three patients, OB was associated with the development of tracheal anastomotic stenosis. Other complications included diabetes mellitus (n = 9), pancreatitis (n = 1) and hypertension (n = 8). Despite these problems, those surviving the first year post-transplant showed a mean FEV1 of 71% (compared to 29% pre-transplant) and enjoyed an overall improved quality of life.

Actuarial Analysis↗

Heart transplantation for dilated cardiomyopathy.

Between 1988 and 1994, 23 patients underwent heart transplantation for dilated cardiomyopathy. The age of the 13 boys and 10 girls was from 8 months to 16 years (mean 7.1 years). Selection criteria included failure to thrive despite maximal antifailure treatment and/or intravenous inotrope dependence. The aetiology of cardiomyopathy was idiopathic (n = 13), congenital (n = 3), anthracycline induced (n = 4), Barth's syndrome (n = 1), and maternal systemic lupus erythematosus (n = 2). The waiting period of heart transplantation ranged from one day to 147 days (mean 22 days). Maintenance immunosuppression included cyclosporin, azathioprine, and prednisolone. Follow up after transplantation was from one month to 62 months (median 27 months) with a mean actuarial survival of 95% at one year and 87% at three years. Four patients developed coronary artery disease, one of whom died as a consequence 15 months after heart transplantation. Heart transplantation has emerged as an acceptable therapeutic option, at least in the short term, for patients with dilated cardiomyopathy.

Adolescent↗

Late outcome of survivors of intervention for neonatal aortic valve stenosis.

BACKGROUND: This study examined the late outcome after intervention for neonatal aortic valve stenosis. METHODS: Seventy-three neonates (59 boys and 14 girls) underwent intervention for critical aortic valve stenosis during the first 30 days of life at two institutions, The Hospital for Sick Children, London, and Duke University Medical Center, Durham, North Carolina. Procedures performed include closed valvotomy (n = 12), open valvotomy with inflow occlusion (n = 14), open valvotomy with cardiopulmonary bypass (n = 33), balloon valvotomy (n = 12), and other procedures (n = 2). The mean age at the first intervention was 8 +/- 1 days. RESULTS: The hospital mortality was 52.1%. The mean duration of follow-up for the hospital survivors (n = 35) was 8.3 +/- 1.1 years. The actuarial survival for the hospital survivors was 93.3% +/- 4.7% at 10 years and 83.9% +/- 9.8% at 15 years, whereas event-free survival (reintervention, endocarditis, or early death) was 61.8% +/- 9.3% at 5 years, 34.2% +/- 10.8% at 10 years, and 27.4% +/- 10.6% at 15 years. Three patients have died and 11 patients have required aortic valve replacement during the follow-up period. The age at the initial intervention, the type of initial intervention, and the year of initial intervention were not predictive of early death or need for reintervention. At last follow-up, 26 of the long-term survivors (n = 32) were in functional class I and 6 were in functional class II. CONCLUSIONS: Aortic stenosis in the neonatal period is a difficult problem with a high initial mortality. Late survival and functional class are excellent for patients surviving the initial hospitalization, but most require further intervention within 10 years.

Aortic Valve Stenosis↗

Tricuspid valve abnormalities in patients with atrioventricular discordance: surgical implications.

From 1975 to 1990, 90 patients (age, 6 months to 30 years; mean, 9.1 years) underwent operation for defects associated with atrioventricular discordance. Twenty-one had an anatomically abnormal tricuspid (systemic) atrioventricular valve (SAVV) of the following types: Ebstein, 11; straddling, 6; and dysplastic, 4. Sixteen valves were regurgitant: regurgitation was trivial to mild in nine and moderate to severe in seven. Two patients underwent a successful Fontan-type operation. None of the 5 patients with a competent SAVV underwent valve repair or replacement; 1 of these patients died. A ventricular septal defect was closed in 14 and an extracardiac valved conduit was placed in 7. Sixteen had a regurgitant valve: it was replaced in 10 and repaired in 2 (early mortality, 25%). All 4 patients who did not undergo repair or replacement of their regurgitant SAVV died. Two patients died late after repeat replacement. Four other reoperations (closure of a residual ventricular septal defect, SAVV replacement, left ventricle-to-pulmonary artery conduit replacement, and a redo Fontan procedure) were successful. Two patients are lost to follow-up, and 9 have been followed up for them 27 to 156 months (median, 117 months). All were well when last seen. We suggest that an abnormal regurgitant SAVV should be replaced. Alternatively, a "double-switch" procedure that leaves the tricuspid valve in the pulmonary circulation may be used.

Adolescent↗